This article examined the role of centering in estimating interaction effects in multilevel structural equation models. Interactions are typically represented by product term of 2 variables that are hypothesized to interact. In multilevel structural equation modeling (MSEM), the product term involving Level 1 variables is decomposed into within-cluster and between-cluster random components. The choice of centering affects the decomposition of the product term, and therefore affects the sample variance and covariance associated with the product term used in the maximum likelihood fitting function. The simulation study showed that for an interaction between a Level 1 variable and a Level 2 variable, the product term of uncentered variables or the product term of grand mean centered variables produced unbiased estimates in both Level 1 and Level 2 models. The product term of cluster mean centered variables produced biased estimates in the Level 1 model. For an interaction between 2 Level 1 variables, the product term of cluster mean centered variables produced unbiased estimates in the Level 1 model, whereas the product term of grand mean centered variables produced unbiased estimates for the Level 1 model. Recommendations for researchers who wish to estimate interactions in MSEM are provided.