The tumour microenvironment plays a dual role in cancer: it can promote tumour progression by establishing pro-tumour survival conditions but can also suppress tumour progression by killing cancer cells or inhibiting their outgrowth. These dynamically interconnected processes are under intense investigation to better understand cancer pathophysiology and allow identification of new therapeutic approaches. The ability of cancer cells to evade anti-tumour T-cell activity in the microenvironment has recently been accepted as a hallmark of cancer progression. This review will highlight the most promising therapeutic approach aimed at activating anti-tumour T-cell immunity in the cancer microenvironment: blocking inhibitory immune regulatory proteins (immune checkpoint ligands and receptors). There is emerging evidence that haematological tumours co-opt immune checkpoints as a major immune resistance mechanism. Pre-clinical findings indicate that targeted therapies and blockade of immune checkpoints could be combined to promote therapeutic synergy and long-term anti-tumour immunity to improve clinical outcomes for cancer patients.