Tick-borne diseases(TBDs) are a major public health concern that has increased in the past three decades. Nevertheless, emerging or reemerging TBDs may be still misdiagnosed. Molecular biology techniques for the screening of ticks, use of \\\"Omics\\\" approaches and the incorporation of analytical methods such as mass spectrometry or nuclear magnetic resonance, to the study of ticks and their associated pathogens or potential pathogens are promising tools for a more accurate differential diagnosis of TBDs. However, this huge amount of data needs to be carefully interpreted before being incorporated to the routine of clinical practice. In the meantime, a clinical approach and high level of suspicion keep being essential for the diagnosis and proper handling of TBDs. Nevertheless, there is a growing body of evidence that tick-borne diseases (TBDs) are a major public health concern that has increased in the past three decades. Nevertheless, emerging or reemerging TBDs may be still misdiagnosed. Molecular biology techniques for the screening of ticks, use of \"Omics\" and the incorporation of analytical methods such as mass spectrometry or nuclear magnetic resonance, to the study of ticks and their associated pathogens or potential pathogens are promising tools for a more accurate differential diagnosis of TBDs. However, this huge amount of data needs to be carefully interpreted before being incorporated to the routine of clinical practice. In the meantime, a clinical approach and high level of suspicion keep being essential for the diagnosis and proper handling of TBDs.