This chapter reviews bicyclic systems containing two fused five-membered rings with one bridgehead nitrogen and two other heteroatoms (nitrogen, oxygen, and sulfur) in each ring. Among the possible structural backbones, 16 have been so far found in the literature. The most abundant literature deals with [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. This chapter details the reactivity and the synthesis of such ring systems. Recent material (published from 1996 to 2005) is essentially focused on biologically active examples of these heterocycles.