Endocannabinoids and endovanilloids are, by definition, endogenous agonists at cannabinoid CB(1) or CB(2) receptors and transient receptor potential vanilloid-type-1 (TRPV1) channels, respectively. Due to the several ways through which cannabinoid receptors influence cytosolic Ca(2+) concentrations, and to the fact that TRPV1 activation leads to the gating of cations, including Ca(2+), both endocannabinoids and endovanilloids, taken separately, can strongly influence Ca(2+) signalling. Moreover, CB(1)/CB(2) receptors and TRPV1 channels are often expressed in the same or neighbouring cells, and this can lead to cross-talk between the two receptor types, which is further enriched by the fact that some endocannabinoids, like anandamide and N-arachidonoyldopamine, also activate TRPV1 channels. Finally, both endocannabinoids and endovanilloids also interact with non-cannabinoid, non-TRPV1 receptors and channels, and, although the full physiological relevance of such interactions is yet to be established, the "promiscuity" of these lipophilic molecules can increase even further the potential ways through which they affect Ca(2+) signalling. Here we discuss the effects of endocannabinoids and endovanilloids on cytosolic Ca(2+) concentrations and their potential biological consequences.