Climate change is projected to aggravate water stress in dry and arid regions. Against the backdrop of the epic drought faced by the U.S. state of California in 2015, this chapter discusses the significant vulnerabilities and options for maintaining the resilience of the state’s water-dependent economic activities. The drought led to very uneven impacts on different water users and sections of the state, as well as on natural ecosystems versus managed landscapes. Differential vulnerabilities can be traced to the state’s complex geography, the configuration of its water storage and delivery infrastructure, and its imperfectly administered mixture of prior appropriation and riparian surface water rights coupled with limited regulation of groundwater withdrawals. Approaches for reducing economic losses have included selective fallowing, increased groundwater pumping, adoption of water-saving irrigation techniques, and market transfers of water. The chapter highlights innovative water management strategies that have emerged over the course of the drought and the lessons that California’s drought experience suggests for other areas that may face increasing drought risks in a warmer future climate.