Arid and semiarid landscapes are often fragile and, thus, vulnerable to both natural weather extremes and human activities. Climate change and increasing demands for food to meet needs of a growing global population will place greater stress on these environments. Cropping and livestock systems have generally succeeded in these regions to the extent that the environment could be altered through water development and irrigation. Water sources for irrigation, including surface and groundwater, are declining in quality and quantity. Improvements in irrigation use efficiency now exceed 95% but often have led to increased water use, instead of water savings, as more systems have been installed. Also, as groundwater becomes scarce, more energy is required to extract water from greater depths. Increasing demands for alternative water uses and depletion of historic water sources make many irrigated systems in dry climates nonsustainable. The Texas High Plains exemplifies these challenges, where agriculture depends heavily on irrigation at non-sustainable rates of water extraction from the Ogallala aquifer. Today, agriculture uses about 95% of total water withdrawn from the aquifer. Crop rotations and integrating crop and livestock systems could reduce irrigation water use and diversify income compared with a monoculture. This region was historically a grazing land ecosystem offering opportunities for pastoral systems and benefits from diversification. Long-term comparisons of two irrigated systems [a cotton (Gossypium hirsutum L.) monoculture and an integrated cotton-forage-beef cattle system] in the Texas High Plains have demonstrated water savings of about 25% achieved through integration, while remaining economically viable and diversifying income sources. Additional benefits included reduced soil erosion, lower chemical inputs including a 40% reduction in N fertilizer, improved soil microbial and enzymatic activities, enhanced C sequestration, and greater rainfall infiltration than the monoculture system. Greater annual crop yields can shift short-term profitability to the monoculture system, but long-term sustainability is likely to depend on environmental benefits and water savings achieved by integrated systems. Challenges include existing large investments in local infrastructure focused on monoculture systems, producer adoption of alternative strategies, enhanced knowledge and management skill required, and a need for more research. Dryland agriculture will increase with remaining water diverted to other uses including livestock, municipalities, manufacturing, and energy generation. Technological advances can increase water savings but can also decrease system resilience with dependence on nonsustainable external buffers. Regional resource and economic stability will likely depend more on internal resilience of appropriately integrated plant and animal agricultural systems.