Ranibizumab (Lucentis(®)), an inhibitor of all vascular endothelial growth factor (VEGF) A isoforms, is approved for the intravitreal treatment of neovascular age-related macular degeneration (AMD). In pivotal trials, monthly injections of ranibizumab were superior to verteporfin photodynamic therapy in the treatment of predominantly classic choroidal neovascularization (CNV) due to neovascular AMD (ANCHOR) and sham in the treatment of minimally classic or occult CNV due to neovascular AMD (MARINA). Monthly or less frequent injections of ranibizumab are generally well tolerated and associated with low rates of ocular and systemic serious adverse events (SAEs). Less frequent dosing has been evaluated with the aim of reducing the burden, risk and cost of monthly injections. In the landmark CATT trial, monthly monitoring and retreatment as-needed with ranibizumab was equivalent to monthly treatment in terms of the vision gain at 1 year, but reduced the number of injections (and the related cost) by approximately one-half. In head-to-head comparisons, aflibercept administered bimonthly was noninferior to ranibizumab administered monthly (VIEW 1 and 2), bevacizumab administered monthly was equivalent to ranibizumab administered monthly (CATT), and bevacizumab administered as-needed was equivalent to ranibizumab administered as-needed (CATT). Bevacizumab is widely used (off-label) for economic reasons; while it was less costly than ranibizumab, it was associated with more systemic SAEs. Notwithstanding the availability of other similarly effective anti-VEGF therapies that are approved (aflibercept) or unapproved (bevacizumab), ranibizumab continues to set the standard as regards the totality of evidence from randomized clinical trials demonstrating its efficacy and tolerability (particularly that of the monthly regimen) in the treatment of neovascular AMD.