Since the 1950’s, the research and industrial communities have developed a body of experimental data and set of analytical tools and correlations for two-phase flow and heat transfer in passages having hydraulic diameter greater than 6 mm or so. These tools include flow regime maps, pressure drop and heat transfer correlations, and critical heat flux limits, as well as strategies for robust thermal management of HVAC systems, electronics, and nuclear power plants. Designers of small systems with thermal management by phase change will need analogous tools to predict and optimize thermal behavior in the mesoscale and smaller sizes. Such systems include a wide range of devices for computation, measurement, and actuation in environments that range from office space to outer space and living systems. This paper examines important proceses that must be considered when channel diameters decrease, including flow distribution issues in single, parallel, and split flows; flow instability in parallel passages; manufacturing tolerances effects; nucleation processes; and wall conductance effects. The discussion focuses on engineering issues for the design of practical systems.