Pharmacotherapy of male sexual dysfunction(s) has developed similar to pharmacotherapy of depression. Some of the treatments for male sexual dysfunctions have been used based on old observations or myths (e.g., so called aphrodisiacs), some based on intuition (e.g. hormones for hypoactive sexual desire disorder), and some were discovered serendipitously (e.g., PDE-5 inhibitors). New, “me-too” PDE-5 inhibitors (e.g., avanafil, mirodenafil, udenafil) are being developed, similar to the development of new antidepressants. A rational approach to pharmacotherapy of hypoactive sexual desire disorder, male erectile disorder and premature ejaculation is being conceptualized (no pharmacotherapy for delayed orgasm is available at present). For instance, the approach to treatment of erectile dysfunction has been frequently staged into three levels (Level I: psychotherapy, oral preparations including hormones, vacuum erectile devices; Level II: intraurethral and intracorporeal application of various preparations; Level III: microsurgery, prosthesis). The management of pharmacotherapy failures, as well as combination of approaches to sexual dysfunctions, (e.g., PDE-5 and hormones for erectile dysfunction) have not been systematically studied. This presentation discusses a rational approach to staging pharmacotherapy of male sexual dysfunction and will also discuss potential combination of therapeutic modalities, especially for treatment resistant cases.