Adequate control of infection relies on development of a tailored immune response according to the requirements of a given infection. This is achieved by the continuous crosstalk between innate and adaptive immunity. Pathogen diversity is deciphered via a plethora of receptors converging signals to adaptor molecules; tissue sites and environment generate additional signals that further influence T cell lineage decisions. Within this continuum of interactions, fine-tuning of the ensuing T cell responses together with plasticity of the committed T cells ensure development of balanced immune responses maintaining homeostasis. This review focuses on the multiple mechanisms that govern T cell differentiation during infection.