In silico binding free energy (FE) calculations using alchemical molecular dynamics (MD) simulations are the current state-of-the-art in computer-aided drug design (CADD), yielding potency estimates that help drive key decisions such as the prioritization of synthesis and testing of candidates in drug discovery. Free energy methods can help save materials and time, potentially leading to more sustainable and efficient drug discovery pipelines. The vast number of successful applications and developments that have been described in the literature back up the use of FE calculations. Many different methods fall within the broader category of free energy calculations.