One in seven men in Australia is at risk of developing prostate cancer before the age of 75. This disease is a leading cause of male death worldwide, with a mortality rate of 62 men per 100,000. Treatments for prostate cancer exist, including surgery, radiotherapy and androgen deprivation therapy. However, the results achieved by the combination of these therapies can lead to variable outcomes, mainly due to the genetic heterogeneity of tumour cells and/or emergence of resistance. In contrast to the cancer cells, the non-cancerous portion of the tumour microenvironment, such as immune cells, fibroblasts and endothelial cells, is a genetically stable target that has a key role in cancer development. Improving our knowledge of the genetic and molecular interactions existing between cancer cells and other non-cancerous cell populations, both in primary or metastatic prostate cancer will provide new key insights in the biology of the disease and give new treatment opportunity.