Background: Depression is one of the most important medical problems in today's world; despite its high prevalence, its causes unfortunately remain not fully known. Among important issues regarding this is its relation with heart diseases. Based on studies this comorbidity increase morbidity and mortality and leads to worst prognosis. However the cause of such high rate of comorbidity is unclear and instead of efforts to understand this correlation has prompted the medical world to consult other medicinal disciplines, not only to find the answer but also to increase the effectiveness of treatment and decrease its cost. Methods: We first reviewed the most important ancient causes for depression mentioned by Avicenna and considered those as the key words for our next step. Then, we made a literature search (PubMed and Scopus) with those key words to find out new scientific findings in modern medicine about the Avicenna's suggestions. Results: Avicenna does not regard depression as only a mental ailment, but as a disorder resulted by the involvement of brain, heart and blood. He believed that the main causes of depressive events are rooted in heart diseases; in most cases brain is only affected secondary to the heart. Thus he declared that for the treatment of depressive disorders, the underlying cardiovascular diseases should be considered. Conclusions: It is worthwhile to consider the Avicenna's recommended causes of depression and to design future scientific studies based on his suggestions.