Mechanistically, photochemistry has an advantage over electrochemistry in the oxidative activation of native functionalities to form radicals. The Ni reduction and oxidative activation do not need to overcome significant diffusion to engage in productive photocatalysis. On the other hand, electrochemistry excels at sequential reductive activation processes. The localized cathodic generation of the key low valent Ni species for substrate activation is easy to attain with the physical separation of redox events in electrochemistry. As the couplings become more ambitious, the critical limitations of Ni-catalysis, regardless of activation methods, are unveiled. For instance, Ni struggles with cross-couplings of sterically demanding alkyl radicals independent of the redox strategy. However, the differences between the two modes of activation reveal staggering differences when starting material access and preparation are considered. When considering the available starting materials for a proposed synthetic sequence, electrochemistry with RAEs appears superior in forging (hetero)aryl C(sp 2 )-C(sp 3 ) linkages with Med-Chem relevant electron-rich heteroarenes. The interference of oxidizable heteroatoms and the requirement of stabilized radicals severely limit an oxidative activation approach from the corresponding alkyl carboxylic acid, despite being a slightly more accessible starting material since no pre-functionalization is required compared to RAEs. However, these limitations of photochemistry are ameliorated by switching starting materials. Alkyl halides and alcohols appear to offer expanded scope compared to their acid counterparts at the cost of substrate synthesis/availability. For instance, the scope of the NHCactivated alcohol C(sp 2 )-C(sp 3 ) cross-coupling is comparable to state-of-the-art RAE chemistry despite requiring a boutique activating handle. Secondary to starting materials accessibility is consideration of the synthetic goal. Within drug discovery, there are two key objectives i) make enough of a substance quickly to interrogate an initial biological hypothesis (mg-scale regime) and, if that compound is exciting, ii) scale up to enable PK across species, PD/efficacy studies, and clinical trials (>decagram needed). Photo-and electrochemistry now offer complementary use cases in modern drug discovery in achieving these key objectives. Photochemistry is easier to scale down to mg-amounts of material. Owing to the latest improvements in instrumentation, photochemical reactions can be run in 24 -384 microwell HTE plates on nano-to milligram scale for library studies and rapid SAR (Structure Activity Relationship) exploration. On the other hand, scaling down electrochemical reactions is challenging owing to the heterogeneous variables (electrode surface/submersion) that need to be considered. Recently, the emergence of high throughput electrochemical reactors is likely to address this practical gap. On the other end of the scale regime, electrochemistry is more scalable than photochemistry. Many of the largest chemical processes are electrochemically driven due to the fine control of reaction parameters, low cost of energy input, and reproducibility. Photochemistry still suffers from light permeation on a large scale and the prohibitive cost of precious metal-based photocatalysts. That being said, flow technologies for photochemistry along with the discovery of new organic-based photocatalysts have emerged as promising solutions to these challenges. Considering the various attributes between the two modes of activation, we encourage researchers in the field to place themselves in the position of the end user of their techn ologies. If a reaction permits access to unprecedented chemical space yet is limited to 15% yield, then such a reaction is useful in the initial testing of a biological hypothesis (early medicinal chemistry) but punts the problem if that compound does become a drug candidate and reliable multi-kilogram amounts are routinely needed (early process chemistry). Contrarily, if a method is routinely high yielding but limited to a certain substrate class, the explorable chemical space for SAR is limited. While limitations initially exist with new methodologies and technologies, academic-industrial partnerships are critical to addressing them, thereby fostering innovation, and promoting cross-disciplinary research endeavors.