A conservative management strategy for knee osteoarthritis is the lateral wedge insole (LWI). The theoretical basis for this intervention is to correct tibiofemoral malalignment, thereby reducing pain and optimising function. This systematic review evaluates the evidence on the effectiveness and safety of LWI for the treatment for knee osteoarthritis. A systematic review was performed, searching published (MEDLINE, AMED, EMBASE, CINAHL, Cochrane Library) and unpublished literature from their inception to August 2012. Randomised controlled trials (RCTs) were included that compared the use of LWI with a neutral insole or control intervention for people with medial compartment osteoarthritis. Risk of bias and clinical relevance were assessed, and outcomes were analysed through meta-analysis. From a total of 3,105 citations, 10 studies adhered to the a priori eligibility criteria. These included 1,095 people; 535 participants were allocated to receive LWI insoles compared to 509 in control groups. Eight per cent of papers were of high quality with low risk of bias. There was no statistically significant difference between LWI and neutral insoles for pain, function, analgesic requirement, compliance or complications (p ≥ 0.07). Those who received LWI demonstrated lower non-steroidal anti-inflammatory drug requirements (p < 0.001). To conclude, there is limited evidence to support the prescription of LWI to people with medial compartment osteoarthritis to reduce pain and increase function. However, there remains a paucity of evidence to determine whether LWI outcomes differ in subgroups of the patients, such as severe compared to mild osteoarthritis, obese patients, or whether the angle of LWI is of clinical importance.