Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.