Following the discovery of cysteinyldopas as the early intermediates in the biogenesis of pheomelanins, the typical red hair pigments, the reactivity of the biosynthetic precursors under biomimetic conditions was extensively investigated. As a result, the early stages of pheomelanogenesis were envisaged as involving oxidative cyclization of cysteinyldopas, mainly the 5-S-isomer, to 1,4-benzothiazine (BTZ) intermediates which undergo oxidative polymerization leading eventually to the pigments. In the last decade, several aspects of the chemistry and biosynthesis of pheomelanins were re-examined. In particular, (i) transient BTZ intermediates were identified by pulse radiolytic techniques and NMR analysis; (ii) the effect of reaction conditions and additives on the rearrangement vs. redox exchange reaction paths of such intermediates were investigated in detail; (iii) the mechanism of the oxidative polymerization of BTZs was characterized by the first isolation of oligomer species, and (iv) the pigment eventually resulting from oxidation of 5-S-cysteinyldopa (CD) was directly analyzed by spectroscopic and chemical methodologies in comparison with pheomelanins isolated from human hair. These advances led eventually to an integrated picture of the biogenetic route highlighting the intervention of various chemical and enzymatic factors which affect the kinetics of the different steps and the nature of the key benzothiazine precursors. A likely biogenetic route was also postulated for the Δ2,2′-bi(2H-1,4-benzothiazine) pigments, termed trichochromes, whose origin had remained an open issue since their first isolation from red human hair and avian feathers. Finally, a more detailed description of the structure of pheomelanin pigments in terms of the monomer units, their mode of linking, and postsynthetic modifications was gained.