Introduction <p>Pharmacokinetics (PKs) of drugs are often altered in the intensive care unit (ICU). Opioids are often used in the ICU, particularly as continuous infusions, and their characteristics lead them to undergo PK alterations. We conducted a systematic review to assess the PK of opioid infusions in the ICU.</p> Methods <p>Embase, MEDLINE, PubMed, CINAHL, and Evidence-Based Medicine Reviews (EBMR) were searched from inception to March 2024. Studies were included if they evaluated PKs of opioid infusions in adult patients in the ICU. Two reviewers independently selected and extracted data.</p> Results <p>Out of the 1040 records screened, 17 studies were included. Five studies were conducted on fentanyl, seven on morphine, one on hydromorphone, two on remifentanil, two on alfentanil, and one on sufentanil. Most studies where observational studies or case series. The mean age was 56 years old. Duration of the infusion varied between 3 h and 20 days. PKs of fentanyl, sufentanil, and hydromorphone were significantly impaired, whereas the PKs of morphine, alfentanil, and remifentanil were impaired to a lesser degree. The PK parameter that was most affected by critical illness was the half-life (<i>T</i>½).</p> Conclusions <p>To counter these PK alterations, new therapeutic avenues must be further explored in the ICU to individualize opioid infusions.</p>