Translating basic scientific discoveries to clinical applications has emerged as an important, but difficult, objective in biomedical research. This bench-to-bedside approach to translational research, however, is really a two-way street. Basic scientists provide clinicians with insights for use in patients, and clinicians make observations about the nature of disease that stimulate basic science investigations. Inherited diseases are prime examples of the latter approach, since the functional analysis of mutated genes may provide important insights into fundamental physiological processes. Polycystic kidney disease (PKD) is a group of inherited diseases characterized by cystic renal tubules. Since mutations in PKD genes cause cysts, the physiological function of these genes must be in controlling tubular morphology. To date more than 30 genes have been identified that cause PKD. Mutations in two genes, PKD1 and PKD2, cause autosomal dominant PKD. PKD1 encodes polycystin-1, a membrane protein that is thought to function as a receptor. Polycystin-2, encoded by PKD2, is a member of the TRP channel family. Both gene products associate to form a receptor-channel complex that triggers calcium signals during tubular morphogenesis. In addition, there are multiple recessive forms of PKD. The manifold PKD gene products share little sequence similarity raising the question about a common mechanism for cystogenesis. Notably, most PKD proteins localize to the primary cilium, a microtubule-based sensory organelle attached to most mammalian cells. An amazing convergence of findings from several species implicates defects in structure and signaling function of primary cilia as a common mechanism in the development of cysts. The study of PKD gene products has revealed fascinating insights into the biology of cilia and tubular morphogenesis but many important questions remain to be answered. A multidisciplinary approach at the interface of genetics, physiology, biochemistry and clinical medicine will be required to address these questions. These studies may ultimately provide the basis for the development of rationale therapies for PKD.