Over the last 10 years, a great boost of knowledge accumulated on the immunomodulatory and anti-inflammatory properties of endocannabinoids (eCBs). In this scenario, these bioactive lipids, which are produced by most immune cells along with a set of receptors and enzymes that regulate their synthesis and degradation, act as secondary modulators and increase or decrease a plethora of immune functions. In this review, the manifold immunomodulatory effects of the main eCBs in different compartments of innate and adaptive immunity will be discussed, suggesting that they could be considered as master regulators of innate-adaptive immune axis and as potent immunoresolvents.