Cancers are not composed merely of cancer cells alone; instead, they are complex 'ecosystems' comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote the resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistromal agents. Herein, we provide an overview of the advances in understanding the complex cancer cell-tumour stroma interactions and discuss how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes.