Monitoring and fault detection methods are increasingly important to achieve a robust and resource efficient operation of wastewater treatment plants (WWTPs). The purpose of this paper was to evaluate a promising machine learning method, Gaussian process regression (GPR), for WWTP monitoring applications. We evaluated GPR at two WWTP monitoring problems: estimate missing data in a flow rate signal (simulated data), and detect a drift in an ammonium sensor (real data). We showed that GPR with the standard estimation method, maximum likelihood estimation (GPR-MLE), suffered from local optima during estimation of kernel parameters, and did not give satisfactory results in a simulated case study. However, GPR with a state-of-the-art estimation method based on sequential Monte Carlo estimation (GPR-SMC) gave good predictions and did not suffer from local optima. Comparisons with simple standard methods revealed that GPR-SMC performed better than linear interpolation in estimating missing data in a noisy flow rate signal. We conclude that GPR-SMC is both a general and powerful method for monitoring full-scale WWTPs. However, this paper also shows that it does not always pay off to use more sophisticated methods. New methods should be critically compared against simpler methods, which might be good enough for some scenarios.