Amblyopia has a 1.6-3.6% prevalence, higher in the medically underserved. It is more complex than simply visual acuity loss and the better eye has sub-clinical deficits. Functional limitations appear more extensive and loss of vision in the better eye of amblyopes more prevalent than previously thought. Amblyopia screening and treatment are efficacious, but cost-effectiveness concerns remain. Refractive correction alone may successfully treat anisometropic amblyopia and it, minimal occlusion, and/or catecholamine treatment can provide initial vision improvement that may improve compliance with subsequent long-duration treatment. Atropine penalization appears as effective as occlusion for moderate amblyopia, with limited-day penalization as effective as full-time. Cytidin-5'-diphosphocholine may hold promise as a medical treatment. Interpretation of much of the amblyopia literature is made difficult by: inaccurate visual acuity measurement at initial visit, lack of adequate refractive correction prior to and during treatment, and lack of long-term follow-up results. Successful treatment can be achieved in at most 63-83% of patients. Treatment outcome is a function of initial visual acuity and type of amblyopia, and a reciprocal product of treatment efficacy, duration, and compliance. Age at treatment onset is not predictive of outcome in many studies but detection under versus over 2-3 years of age may be. Multiple screenings prior to that age, and prompt treatment, reduce prevalence. Would a single early cycloplegic photoscreening be as, or more, successful at detection or prediction than the multiple screenings, and more cost-effective? Penalization and occlusion have minimal incidence of reverse amblyopia and/or side-effects, no significant influence on emmetropization, and no consistent effect on sign or size of post-treatment changes in strabismic deviation. There may be a physiologic basis for better age-indifferent outcome than tapped by current treatment methodologies. Infant refractive correction substantially reduces accommodative esotropia and amblyopia incidence without interference with emmetropization. Compensatory prism, alone or post-operatively, and/or minus lens treatment, and/or wide-field fusional amplitude training, may reduce risk of early onset esotropia. Multivariate screening using continuous-scale measurements may be more effective than traditional single-test dichotomous pass/fail measures. Pigmentation may be one parameter because Caucasians are at higher risk for esotropia than non-whites.