S-acylation (or palmitoylation) is a reversible post-translational modification (PTM) that modulates protein activity, signalization and trafficking. Palmitoylation was found to significantly impact the activity of various membrane receptors involved in either pathogen entry, such as CCR5 (for HIV) and anthrax toxin receptors, cell proliferation (epidermal growth factor receptor), cardiac function (β-Adrenergic receptor), or synaptic function (AMPA receptor). Palmitoylation of these membrane receptors indeed affects not only their internalization, localization, and activation, but also other PTMs such as phosphorylation. In this review, we discuss recent results showing how palmitoylation differently affects the biology of these membrane receptors.