The article is an up-to-date review of the state-of-the art in the challenging field of smart synthetic polymer nanocarriers, presenting the most relevant achievements in the area, with a special emphasis on the outstanding potential of these nanovehicles to be used as multifunctional devices capable to deliver their cargo to a specific targeted area in the human body and to release it in a well controlled fashion. Stimuli-responsive nano drug delivery systems are presented according to a classification that takes into account the endogenous or exogenous nature of the stimuli. Each category is amply illustrated by carefully selected examples of the most impressive achievements. The endogenous stimuli category is fully described by presentation of pH, redox potential, and enzyme-responsive nanocarriers. From the category of exogenous stimuli-responsive nanomaterials, we focused our attention on temperature, light and magnetic sensitive nanocarriers.