Over the past 10 years, the number of targeted therapies for haematological malignancies has substantially increased, and many new drugs have entered the market. Many of these therapies have shown improved disease-free survival and reduced toxicity compared with existing treatments, especially in older patients. However, most of these new drugs undergo extensive hepatic metabolism and exhibit moderate to severe drug–drug interactions with triazole antifungal agents, which are essential for the prophylaxis and long-term treatment of invasive fungal infections. In this Review, we give a comprehensive overview of all known drug–drug interactions between new targeted drugs for haematological malignancies and antifungal drugs, in particular the triazoles. We begin with a general background on drug–drug interactions. Next, we provide a management strategy for the use of each targeted haematological drug, and discuss the possible role of therapeutic drug monitoring for both the triazole and the haematological drugs. This Review aims to provide practical guidance to clinical haematologists on managing the complex interplay between targeted therapies for haematological malignancies and triazole antifungal drugs, to pursue better outcomes for their patients.