A closer look at naturally occurring polyyne compounds reveals some fascinating elements of molecular architecture. These structurally unique classes of compounds, as well as a host of analogs, exhibit a variety of biological effects, including antimicrobial, anti-inflammatory, antitumor, antiangiogenic and anti-HIV activities. The distinct biological activities of these molecules have motivated synthetic organic chemists worldwide to plane and execute their total syntheses. Most natural polyynes pose a substantial synthetic challenge because of their highly unsaturated nature. This book recounts these synthetic achievements and also highlights both the natural source(s) and biological relevance for many of these compounds.