Melanoma is a type of skin cancer that occurs when melanocytes, melanin-producing cells located in the epidermis, start proliferating in an uncontrolled manner. It is the deadliest form of skin cancer, affecting a higher number of people each year. Despite remarkable efforts, current therapies fail mainly because tumours rapidly develop drug resistance. Research should focus on further understanding the mechanisms underpinning advanced-stage melanoma as well as identifying predictive and prognostic biomarkers in order to satisfy the need for better treatments and overcome drug resistance. In addition, the major challenge for future drug development also comprises finding alternative models for drug screening purposes.