Lithium is a critical and technologically important element that has widespread use, particularly in batteries for hybrid cars and portable electronic devices. Global demand for lithium has been on the rise since the mid-1900s and is projected to continue to increase. Lithium is found in three main deposit types: (1) pegmatites, (2) continental brines, and (3) hydrothermally altered clays. Continental brines provide approximately three-fourths of the world’s Li production due to their relatively low production cost. The Li-rich brine systems addressed here share six common characteristics that provide clues to deposit genesis while also serving as exploration guidelines. These are as follows: (1) arid climate; (2) closed basin containing a salar (salt crust), a salt lake, or both; (3) associated igneous and/or geothermal activity; (4) tectonically driven subsidence; (5) suitable lithium sources; and (6) sufficient time to concentrate brine. Two detailed case studies of Li-rich brines are presented; one on the longest produced lithium brine at Clayton Valley, Nevada, and the other on the world’s largest producing lithium brine at the Salar de Atacama, Chile.