Initially described in 1959 as a technique to measure left atrial pressures, and later used during balloon mitral valvuloplasty, transseptal puncture (TSP) is frequently the access route for procedures involving the left heart chambers. Currently, it is mostly used in electrophysiology laboratories for arrhythmia ablation and during left atrial appendage occlusion procedures. However, with the ongoing development of percutaneous mitral valve interventions, it is expected that a greater number of interventional cardiologists will be using this technique in the near future. In this article, we review the technique for performing TSP safely, and we provide recommendations and different strategies to deal with difficult TSPs.