The present overview is a systematic synthesis of the existing research evidence on IOP-lowering treatment modalities for POAG. For this purpose, systematic reviews/meta-analyses of high quality primary trials were retrieved by a thorough and sensitive search of electronic databases. Quality of evidence was assessed using validated tools, and conclusions were derived from the best available evidence. Twenty systematic reviews/meta-analysis out of 1608 records identified initially met the inclusion criteria, but only seven provided evidence of at least moderate quality. Available evidence indicated that the three evaluated prostaglandin analogues (PGAs) were equivalent regarding IOP lowering effect, but latanoprost was tolerated better. In respect to IOP lowering effect, non-PGA medications did not relevantly differ between each other, but they were less effective compared to PGAs. Combination therapy of latanoprost and timolol showed higher effect than their individual treatments. Evidence on the effect of treatments on VF and ONH changes and that on adverse events was of lower quality, therefore no conclusions could be made.