Ongoing regulation of, and concerns regarding, per- and polyfluoroalkyl substances (also popularly known as “highly fluorinated chemicals”), has driven the textile market to search for sustainable alternative chemistries that can provide similar liquid repellency to per- and polyfluoroalkyl substances in performance textiles. This paper aims to inform the potential substitution of fluorochemicals with more environmentally friendly durable water repellents, taking a case-by-case approach and evaluating protection needs for consumer outdoor clothing and medical protective clothing separately. Recently developed non-fluorinated durable water repellents, some based on green chemistry principles, were evaluated in an in-depth assessment for their functionality against fluorinated short-chain alternatives (with hydro-and oleophobic moieties of carbon chain length of six or less). Repellency towards water and non-polar liquids was evaluated with established standard test methods and by measuring the roll-off angle of liquid droplets with a novel sample holder setup. This improved method allowed an enhanced mechanistic understanding of the droplets’ roll-off processes on woven textiles. The best non-fluorinated alternatives demonstrated high water repellency equal to fluorinated side-chain polymers with ‘short’ fluorinated carbon chains ≤6 carbons, and should be considered as suitable substitutes for consumer outdoor clothing. These results are supported by a survey of end-use requirements indicating water repellency and durability were the most important purchasing criteria. For polar liquids, with lower surface tensions, the repellency provided by non-fluorinated alternatives was clearly reduced, although they had a moderate repellency towards liquids with intermediate polarity (e.g. red wine or synthetic blood). Only fluorinated side-chain polymers with ‘short’ fluorinated carbon chains ≤6 carbons were seen to provide sufficient protection to polar liquids with very low surface tension (olive oil or gastric fluid). Since occupational protective clothing (e.g. medical clothing) often must provide protection against liquid of a wider range of polarities (e.g. in the case of medical clothing, to bodily fluids and protect the wearer from the transmission of diseases), current non-fluorinated DWRs do not provide sufficient liquid repellency. This implies that innovations in textile technology are still needed to substitute PFASs in some types of occupational protective clothing and other end uses where oil and stain repellency is essential.