Structure-Based Drug Design (SBDD) has been in use within the pharmaceutical industry for over twenty five years. SBDD continues to play an important role in drug discovery, design and optimization. Moreover, with the development of sophisticated biophysical and computational methodologies SBDD is impacting hit identification and 'hit to lead' optimization approaches across the industry. In this program, we wish to highlight some recent breakthrough stories and successes using SBDD driven by medicinal chemistry, computational and biophysical approaches.