The reliability of process analytical technology (PAT) methods depends on how samples are obtained. The results obtained will not be reliable if the material next to the sensor probe is not representative of the lot or batch being monitored. PAT methods must be implemented so that all parts of the lot have an equal opportunity to be sampled. This Stimuli article summarizes a set of sampling unit operations and governing principles that have been developed as part of the theory of sampling (TOS). TOS can be applied to PAT as described in this article. The application of TOS principles will increase the reliability of PAT results. The adoption of the approaches described in this article will help reduce sampling errors and improve product quality.