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Background: Pasireotide is a second-generation somatostatin (SRIF) receptor ligand (SRL), approved for medical treatment of acromegaly and Cushing's disease (CD). The molecule is a stable cyclohexapeptide synthetized based on SRIF structure. Differently from first-generation SRLs (e.g. octreotide), preferentially binding somatostatin receptor (SST) subtype 2 (SST 2 ), pasireotide has high affinity for multiple SSTs (SST 5  > SST 2  > SST 3  > SST 1 ). Interestingly, early preclinical studies demonstrated that pasireotide shows distinct functional properties compared to SRIF and first-generation SRLs when binding SSTs., Methods: We aimed to highlight the differential receptor-targeted action of pasireotide in the treatment of somatotroph and corticotroph adenomas, throughout the critical revision of preclinical studies carried out on acromegaly and CD models., Results: Different authors demonstrated that the antisecretory effect of pasireotide in somatotroph adenoma cell cultures is comparable to that of the SST 2 -preferential agonist octreotide. Some reports even show a direct correlation between SST 2 mRNA expression and GH reduction after pasireotide treatment, thus laying for a predominant role of SST 2 in driving pasireotide efficacy in somatotropinomas in vitro. On the other hand, the inhibitory effect of pasireotide on ACTH secretion in corticotropinoma cells seems to be mainly mediated by SST 5 . Indeed, most reports show a higher potency and efficacy of pasireotide compared to SST 2 preferential agonists, while functional studies confirm the pivotal role of SST 5 targeting in corticotroph cells., Conclusions: The analysis of preclinical studies carried out in somatotroph and corticoph adenomas points out that pasireotide shows a cell-specific activity, exerting its biological effects via different SSTs in the different adenoma histotypes.