Deregulation of Toll-like receptor (TLR) mediated responses can have devastating effects on the host if left unchecked. It is, therefore, critical that control is exerted at several levels. In this review, we discuss post-translational modification of TLRs and their associated signaling molecules as one such means of control. In particular, we focus on the phosphorylation, ubiquitination and de-ubiquitination of various components of TLR signaling pathways.