The aetiology of childhood asthma is complex. An early dysfunction in the immunological development of the innate immune system in combination with environmental factors possibly triggers asthma. CD14 and toll-like receptors are important components of the innate immune system. The aim of this systematic review was to obtain a better insight into the relation between CD14 and toll-like receptors and childhood asthma in Caucasians. We searched PubMed and EMBASE for relevant articles. In total, 44 articles were included. The quality of the selected studies was independently assessed by the first two authors using the Newcastle-Ottawa quality assessment scale. Toll-like receptor 2, toll-like receptor 6, toll-like receptor 9, and toll-like receptor 10 appear to have some association with childhood asthma in Caucasians. The evidence for a relation of CD14 with childhood asthma is limited. In conclusion, there is no convincing evidence yet for a role of CD14 and toll-like receptors in relation to childhood asthma. Future studies should include haplotype analysis and take environmental factors into account to further clarify the role of CD14 and toll-like receptors on childhood asthma.