The two most commonly used techniques in clinical use are the loss of resistance to air and to normal saline. The term loss of resistance refers to the subjective feel of a change in resistance while the epidural needle penetrates the interspinous ligament, the ligamentum flavum, and subsequently into the epidural space. This chapter evaluates whether, during the loss of resistance technique, air or saline used during epidural anesthesia influences either the efficacy of regional blockade or the incidence of complications such as accidental dural puncture rate and postdural puncture headache (PDPH). There are few prospective, controlled, randomized double-blind trials comparing the complications of air vs. saline in identifying the epidural space. Using saline as part of a loss of resistance technique to identify the epidural space is probably the most widely accepted practice worldwide among anesthesiologists.