Achieving and maintaining therapeutic levels of analgesic medications while avoiding adverse drug reactions in seriously ill patients are challenges faced by all critical care practitioners. A sound knowledge of the pharmacokinetic and pharmacodynamic characteristics of analgesic drugs enables clinicians to optimize use of these agents. An understanding of the physiological alterations in critically ill patients and their effects on pharmacokinetics and pharmacodynamics is also important for the management of pain in the intensive care unit (ICU). Opioid narcotic drugs, including fentanyl and morphine, are the most commonly used analgesic agents in the critical care setting and are administered by several different routes using many different dosing techniques and schedules. Intravenous (IV), intramuscular (IM), transdermal, oral, intranasal, rectal, epidural, and intrathecal routes have all been utilized for analgesic drugs in the ICU and are associated with different advantages and disadvantages. Different dosing techniques including continuous infusion, intermittent bolus, and patient-controlled analgesia (PCA) have all been employed in the ICU. This article describes general pharmacokinetic and pharmacodynamic principles, different routes and techniques for administering analgesic medication, pharmacokinetic parameters for commonly used analgesic drugs, and pharmacokinetic and pharmacodynamic alterations in ICU patients.