This chapter provides the biological background of the research regarding chronic lymphocytic leukemia (CLL) and toll‐like receptor (TLR) pathways. Stimulation of TLRs induces an immediate signaling cascade resulting in the production of inflammatory cytokines and the expression of costimulatory molecules. The chapter then describes the theory and methodology regarding structural equation modeling (SEM). Structural equation models can generally be interpreted as carriers of substantive causal or probabilistic information. In SEM theory, there are two categorizations of variables: exogenous and endogenous and latent and observed variables. The chapter also presents the application of the method to a data set by building models and estimating the causal relationships of the variables. It examines the relationships among genes included in the TLR signaling pathway, from a statistical point of view. The goal is to track interactions between genes, which translates into finding causality relations using a statistical method, in particular, SEM.