Blepharitis is an eyelid disorder characterized by inflammation and pain. It affects all the ages and ethnic groups. Primary cause of blepharitis is poor hygienic condition. Topical antibiotics are the preferred first line therapeutic agents along with eyelid cleansing and warm compresses are recommended. Topical steroids, oral antibiotics and calcineurin inhibitors are also recommended in severe conditions. However, recurrence of disease, dose related side effects and safety regimen are still uncertain with these agents. Blepharitis needs a long term treatment, thus novel formulations and products with natural components may be considered more reliable to overcome such issues. In this review article we have discussed human clinical trials (HCTs) conducted with conventional synthetic drugs, novel drug delivery systems developed with synthetic drugs and drugs of natural origin and other supportive measures. As compared to synthetic drugs, formulations with natural origin were found to be safe with minimum side effects.