In this review, I describe various natural manifestations of purine systems, i.e., methylated, higher-alkylated, and glycosylated forms. These comprise the purine alkaloids, cytokines, as well as the purine nucleoside antibiotics. In part, the compounds described herein were isolated from natural sources already long ago. However, some have been reported only during the last few years. The biological activities of most of the purine derivatives are briefly described, and, in some cases, syntheses are formulated. In particular, this article introduces the main synthetic principles for the generation of the purine ring system. The last chapter describes modern preparative routes for C-alkylation and C-arylation of purines.