Abstract:Objective. This paper presents an overview of generalizable and explainable artificial intelligence (XAI) in deep learning (DL) for medical imaging, aimed at addressing the urgent need for transparency and explainability in clinical applications. Methodology. We propose to use four CNNs in three medical datasets (brain tumor, skin cancer, and chest x-ray) for medical image classification tasks. In addition, we perform paired t-tests to show the significance of the differences observed between different methods. Furthermore, we propose to combine ResNet50 with five common XAI techniques to obtain explainable results for model prediction, aiming at improving model transparency. We also involve a quantitative metric (confidence increase) to evaluate the usefulness of XAI techniques. Key findings. The experimental results indicate that ResNet50 can achieve feasible accuracy and F1 score in all datasets (e.g., 86.31\% accuracy in skin cancer). Furthermore, the findings show that while certain XAI methods, such as XgradCAM, effectively highlight relevant abnormal regions in medical images, others, like EigenGradCAM, may perform less effectively in specific scenarios. In addition, XgradCAM indicates higher confidence increase (e.g., 0.12 in glioma tumor) compared to GradCAM++ (0.09) and LayerCAM (0.08). Implications. Based on the experimental results and recent advancements, we outline future research directions to enhance the robustness and generalizability of DL models in the field of biomedical imaging.