The emergence of marine toxins such as ciguatoxins (CTXs) and tetrodotoxins (TTXs) in non-endemic regions may pose a serious food safety threat and public health concern if proper control measures are not applied. This article provides an overview of the main biorecognition molecules used for the detection of CTXs and TTXs and the different assay configurations and transduction strategies explored in the development of biosensors and other biotechnological tools for these marine toxins. The advantages and limitations of the systems based on cells, receptors, antibodies, and aptamers are described, and new challenges in marine toxin detection are identified. The validation of these smart bioanalytical systems through analysis of samples and comparison with other techniques is also rationally discussed. These tools have already been demonstrated to be useful in the detection and quantification of CTXs and TTXs, and are, therefore, highly promising for their implementation in research activities and monitoring programs.