Peptides are short poly-amide chains formed from amino acids. Playing vital roles in various biological processes, peptides function as hormones, neurotransmitters, growth factors, and defensins. Peptide synthesis is critical for exploring such activities and for harnessing the polyamide structure to develop therapeutics. As therapeutics, peptides offer attributes including high potency and low toxicity combined with drawbacks such as limited bioavailability and rapid metabolism. Chemical modifications to overcome such limitations can add additional synthetic challenges. The advent of solid-phase peptide synthesis (SPPS) provided an effective method for procuring peptides due in part to ability to automate a process in which excess reagent could be employed to drive reactions to completion and by-products could be removed by simple filtration. Solid-and liquid-phase peptide synthesis (SPPS and LPPS) have become widely used platform technologies for product procurement; however, these methods commonly lack atom economy and possess relatively high process mass intensity (PMI) raising environmental concerns. Compared to that of small molecules, the average PMI for SPPS is approximately 40 to 80 times more intensive. Moreover, SPPS has a PMI that is nearly twice as large as that for the making of biopharmaceuticals. Efficient and environmentally friendly methods are required to overcome the high PMI in peptide manufacturing, which is distributed over the synthesis and purification steps to provide pure product. With the growing use of peptides in pharmaceuticals, demand increases for more optimal synthetic and purification manufacturing technologies. Typically, SPPS is performed by linking the carboxylate terminal to the resin and elongation in the Cto N-direction. A key advantage of such an approach has been ability to minimize racemization through the employment of carbamate nitrogen protecting groups. The advantages of carbamates are however balanced by the waste produced in repetitively using such temporary protection in the synthetic process. In contrast, nature synthesizes peptides in the amine to carboxylate Nto C-direction relying heavily on the ribosome to ensure that amide bond formation proceeds without racemization. In the history of solid-phase peptide synthesis, the Nto C-direction elongation approach originated at the same time as the more well practiced Cto N-method. A recent renaissance of methods for Nto C-peptide synthesis without racemization has emerged driven in part by desires for more environmentally friendly manufacturing. This overview is intended to provoke alternative thinking by highlighting developments in methods for Nto C-peptide synthesis. Clemency is entreated for lack of comprehensiveness and for including research performed in 2000 within the twentieth century perspective because of a relationship to earlier related methods. In reviewing historical and recent methods, perspective is offered for reconsidering a different more natural direction for sustainable peptide production.