Midline catheters have recently gained popularity in clinical use, with a common reason being the reduction of central venous catheter use and central line-associated bloodstream infections. At the same time, the number of nononcology vesicant medications has increased, and midline catheters are frequently being used for infusions of vesicant medications. The Infusion Nurses Society (INS) Vesicant Task Force identified midline catheter use as a possible risk factor for extravasation and concluded that a thorough literature review was necessary. This review highlights the variations in catheter terminology and tip locations, the frequency of infiltration and extravasation in published studies, and case reports of infiltration and extravasation from midline catheters. It also examines the many clinical issues requiring evidence-based decision-making for the most appropriate type of vascular access devices. After more than 30 years of clinical practice with midline catheters and what appears to be a significant number of studies, evidence is still insufficient to answer questions about infusion of vesicant and irritant medications through midline catheters. Given the absence of consensus on tip location, inadequate evidence of clinical outcomes, and importance of patient safety, the continuous infusion of vesicants, all parenteral nutrition formulas, and infusates with extremes in pH and osmolarity should be avoided through midline catheters.