Modern lettuce production systems are dominated by the need to produce a high-quality product cost-effectively. However, environmental and human health considerations are increasingly important with regard to the use of water, fertilizer and pesticides and are driving particular developments in the lettuce production system. Some of these drivers are already, or will be, exacerbated by climate change. There is an important role for plant breeding in terms of responding to market requirements for novel salad products and to address the need to reduce inputs. This chapter looks at recent advances in lettuce cultivation. Sections are provided on crop nutrition, irrigation and crop protection. Pesticidal control, host-plant resistance and other methods of control are also discussed with each of these sections considering weeds, pests and diseases. The chapter concludes with an exploration of novel production systems for lettuce including hydroponic production systems, and precision farming and automation.