Adequate venous access is an essential component of therapeutic plasma exchange (TPEX). The simplest kind of venous access is venipuncture of antecubital veins, but this technique may be limited by venous size or scarring following the procedure, requiring the placement of a specialized vascular access device (VAD). VADs provide reliable central venous access and may remain in place for several weeks or months, depending on the VAD and the venous site chosen. Their use, however, is potentially limited by the risk of complications. We discuss indications for insertion, choice of catheter and access site, and complications of VAD placement for TPEX.