Castration-refractory prostate cancer (CRPC) makes up 5-20% of all prostate cancer (PCa) cases. Basically the reason for CRPC is a regulation breakdown of the androgen receptors (AR). The altered ARs are seldom to see in the untreated cases, which stands for the role of the hormonal therapy on these AR changes. One of the perspective directions in the CRPC treatment is a combination therapy using somatostatin analogues (octreotide) and dexamethasone. Somatostatin plays an important role in the physiology of different organs, including prostate. Somatostatin receptors are the potential target during prostate cancer treatment. Somatostatin analogues (for example, octreotide) inhibit the growth of the PCa in vitro, showing indirect anti-hormonal action (due to feedback loop) and direct anti-mitotic effect related to the inhibition of the SSTR type 2-5. A rationale for the anti-tumor action of the somatostatin analogues could be the inhibition of the cell growth and of the tumor angiogenesis, so as promotion of the tumor cell apoptosis. The patients with CRPC are being treated with the second-line hormonal therapy (estrogens, ketoconazole), which are in general far from ideal substances in terms of efficacy and tolerability. This was a main trigger to seek for other treatment modalities. One of the medications is Octreotide-Depo, which is an somatostatin analogue by nature, intended to have a direct and indirect anti-tumor action on the PCa cells. Current evidence shows the high efficacy of the combination therapy in patients with CRPC using Octreotide-Depo and dexamethasone and a good tolerability profile with low rate of side effects in the majority of patients.