Intragastric drug release from solid oral dosage forms can be affected by altered physicochemical and mechanical conditions in the upper gastrointestinal (GI) tract. Food effects may lead to changes of one or more pharmacokinetic parameters and, hence, influence drug plasma levels. This can result in severe consequences such as adverse drug reactions or even therapy failure. This review highlights different examples of drug performance under fed conditions. Various reasons such as delayed gastric emptying and pH-dependent solubility of the API as well as intragastric location and movement profiles of solid dosage forms can account for changed drug dissolution. Over the past years, several biorelevant media (e.g., fed state simulated gastric fluid) have been developed with the aim to approach the physiological situation regarding parameters such as pH, buffer capacity, surface tension, and osmolality. It was shown in different in vitro experiments that all of these factors can have an impact on drug dissolution. Besides the application of complex media such as milk or nutritional drinks, the dynamic changes of the gastric content were depicted in recent studies. The capabilities, limitations, and applicability of newly established test setups for the biorelevant simulation of intragastric drug delivery behavior are discussed. Simple test devices (e.g., rotating beaker or dissolution stress test) are mainly used for the biopharmaceutical evaluation of certain problems such as the impact of pressure or shear forces. On the other hand, complex biorelevant test devices (e.g., TNO TIM-1, Dynamic Gastric Model) have recently been introduced aiming at the simulation of multiple parameters characteristic for the postprandial upper GI tract. The different test methods are reviewed with respect to the spectrum of the simulated physiological factors and the degree of complexity.