The number and complexity of endoscopic gastrointestinal diagnostic and therapeutic procedures is globally increasing. Procedural analgosedation during gastrointestinal endoscopic procedures has become the gold standard of gastrointestinal endoscopies. Patient satisfaction and safety are important for the quality of the technique. Currently there are no uniform sedation guidelines and protocols for specific gastrointestinal endoscopic procedures, and there are several challenges surrounding the choice of an appropriate analgosedation technique. These include categories of patients, choice of drug, appropriate monitoring, and medical staff providing the service. The ideal analgosedation technique should enable the satisfaction of the patient, their maximum safety and, at the same time, cost-effectiveness. Although propofol is the gold standard and the most used general anesthetic for endoscopies, its use is not without risks such as pain at the injection site, respiratory depression, and hypotension. New studies are looking for alternatives to propofol, and drugs like remimazolam and ciprofol are in the focus of researchers’ interest. New monitoring techniques are also associated with them. The optimal technique of analgosedation should provide good analgesia and sedation, fast recovery, comfort for the endoscopist, patients’ safety, and will have financial benefits. The future will show whether these new drugs have succeeded in these goals.