Early descriptions of the plasma membrane depicted it as a fluid layer of lipids hosting freely diffusing proteins without implying any spatial organization. Over the past decades, a different picture is arising describing the plasma membrane as rich in compartments heterogeneous in their biophysical properties and components. Compartmentalization of the plasma membrane into specialized regions seems to play a role in the regulation of several biological functions. Two major drivers of compartmentalization have been described so far: heterogeneities in the local curvature of the plasma membrane and lateral heterogeneities in the distribution of lipids. In this thesis, we have studied plasma membrane heterogeneities from two distinct perspectives. First, we focused on obtaining mechanistic insights on how the curvature of the plasma membrane is regulated. Specifically, we investigated the sensing and generation of membrane curvature by two inverse bin/amphiphysin/rvs (I-BAR) domains in the plasma membrane of living cells. Second, we analyzed the persistency of lateral heterogeneities within the plasma membrane by evaluating their impact on the oligomerization of G-protein coupled receptors (GPCRs).