Prostaglandin analogs (PGA) have been the initial treatment of choice in many patients with glaucoma. However, there is an increasing awareness that non adherence and disruption of the ocular surface may limit PGA utility and tolerability respectively in some patients. In an eye with an open iridocorneal angle, these issues can potentially be addressed with the use of laser trabeculoplasty (LT). This therapy can achieve long-term intraocular pressure reduction following 1 to 2 treatment sessions without the ongoing need to apply medication (and preservatives) to the ocular surface. Whether PGAs or LT should be used in a given individual will also be influenced by other important factors including efficacy, response rate, tolerability, complications, cost and accessibility. This review examines these issues in relation to the initiation of primary therapy.