Multiple interacting checkpoints are involved in the pathophysiology of gout. Hyperuricemia is the key risk factor for gout and is considered a prerequisite for monosodium urate (MSU) crystal formation. Urate underexcretion through renal and gut mechanisms is the major mechanism for hyperuricemia in most people. Multiple genetic, environmental, and metabolic factors are associated with serum urate and alter urate transport or synthesis. Urate supersaturation is the most important factor for MSU crystal formation, and other factors such as temperature, pH, and connective tissue components also play a role. The nucleotide-binding oligomerization domain leucine-rich repeats and pyrin domain-containing protein 3 inflammasome plays a pivotal role in the inflammatory response to MSU crystals, and interleukin 1β is the key cytokine mediating the inflammatory cascade. Variations in the regulatory mechanisms of this inflammatory response may affect an individual's susceptibility to developing gout. Tophus formation is the cardinal feature of advanced gout, and both MSU crystals and the inflammatory tissue component of the tophus contribute to the development of structural joint damage owing to gout. In this article, we review the pathophysiologic mechanisms of hyperuricemia, MSU crystal formation and the associated inflammatory response, tophus formation, and structural joint damage in gout.