Laboratory diagnostics is an integral part of the diagnostic process, providing healthcare professionals with objective data for making clinical decisions. In recent years, technological innovations and advancements in laboratory medicine have opened new horizons for their application in practical healthcare, significantly improving clinical laboratory diagnostics and contributing to its transition to a new level. At the same time, errors that occur at various stages of clinical laboratory studies can lead to diagnostic mistakes, devaluing the achievements in laboratory medicine and causing iatrogenic harm to patients. The critical role in the reliability of laboratory test results belongs to the pre-analytical phase. At this stage, the overwhelming majority of errors in the laboratory diagnostic process occur, which are the main reason for sample rejection and continue to be a serious problem today. The primary cause of pre-analytical errors is the acquisition of poor-quality samples, with hemolysis of blood being the main factor for sample rejection. Hemolysis occurs due to violations of blood sampling, storage, transportation, and initial processing rules. Thus, the human factor plays a key role in obtaining poor-quality samples, and hemolyzed samples represent a significant challenge for laboratory specialists worldwide. Addressing these issues is crucial for ensuring the quality of laboratory research, diagnostics, and improving patient treatment outcomes. The review presents a comprehensive analysis of the causes of hemolysis and its consequences for clinical laboratory diagnostics. In addition, issues of hemolysis interference are discussed, along with recommendations to eliminate or minimize the rejection of samples due to obtaining hemolyzed specimens, as well as strategies to improve the quality of blood samples. Considering the high prevalence of hemolyzed blood samples and the associated healthcare costs, measures aimed at addressing this significant problem are justified and have great potential.