'First line' treatments used for treatment of sexual dysfunctions fail from time to time. As sexual medicine is becoming medicalized, the first reaction to treatment failure of medications such as phosphodiesterase-5 inhibitors is an attempt to use another, mostly older and more invasive medication (e.g., intracavernosal alprostadil). This approach seems intuitively correct but may contribute to patient dissatisfaction and demoralization and later on to continuation of treatment failures. One of the possible reasons contributing to treatment failures is the lack of using psychotherapy and sex therapy, either alone or in conjunction with biological treatments. I propose that after a thorough evaluation, psychoeducation and modification of lifestyle, patients suffering from sexual dysfunction should begin sex therapy/psychotherapy for her/his dysfunction together with medication, if it is clearly indicated. If the first line biological treatment fails, therapy should continue focusing on the underlying cause(s) and possible reasons for biological treatment failure before one starts another medication. Psychotherapy and sex therapy may also help to address various issues contributing to treatment failure, such as a) non-adherence to biological treatments, b) interpersonal issues, c) substance abuse, and even d) cultural issues.