The weaning period is a very stressful event for the piglet that can impact the health, welfare and performance. This period of transition is characterized by the adaptation of newly weaned piglets to their new environment, diet, changing in their immunological status and pathogens circulation that can impact their following performance. Knowledge of main risk factors and the measures necessary to prevent health problems is of fundamental importance for a better management of this delicate phase in the pig's production path. A large part of the chapter is devoted to the discussion of factors influencing health and performance of pigs and related intervention and prevention strategies to be implemented in the period of transition from weaning. A more specific section, in the second part of the chapter, takes into consideration the main etiological agents acting in the period of transition from weaning, the risk factors for their introduction and diffusion within the farm, and the main measures for their control.