Mechanical ventilation is an integral part of the critical care environment and requires orchestration by a multidisciplinary team of clinicians to optimize therapeutic outcomes. By tradition, pharmacists have not been included on this team since this therapeutic modality is not considered relevant to their scope of practice. However, pharmacists play a critical role in the management of patients receiving mechanical ventilation by assisting in the development of institutional guidelines and protocols, by maintaining accuracy of prescribed drug dosages, by monitoring for drug-drug and drug-disease interactions, by assisting with alternative drug selections, and by maintaining continued quality assessment of drug administration. Pharmacists able to understand and integrate mechanical ventilation with the pharmacotherapeutic needs of patients are better qualified practitioners. The goal of this article is to help clinical pharmacists better understand the complexities of mechanical ventilation and to apply this information in optimizing delivery of pharmaceutical agents to critical care patients.