CRISPR-based genome editing has transformed life sciences and human medicine by enabling precise modification of genetic material. This review discusses current CRISPR technologies, their limitations, and recent innovations. It highlights applications in human health and therapeutics, and outlines future developments. CRISPR-Cas9, derived from prokaryotic defense systems, revolutionized genome editing with its programmability and efficiency. It enables site-specific DNA cleavage, leading to gene knockouts, insertions, or deletions via DNA repair pathways. However, off-target effects and limited PAM requirements restrict its scope. Recent advancements include high-fidelity Cas9 variants, modified guide RNAs, and alternative PAM-targeting enzymes. Base and prime editing technologies allow precise single-nucleotide or small DNA sequence modifications without DSBs. These innovations enhance specificity and reduce off-target effects. CRISPR also enables transcriptional modulation through dCas9 fusions, allowing gene activation or suppression. RNA-guided Cas13 enzymes offer tools for RNA editing and modification. CRISPR applications span basic research, disease modeling, and therapeutic interventions, including gene therapy for genetic disorders. Ex vivo and in vivo approaches are being developed for clinical use. Large animal models, such as non-human primates, pigs, and dogs, provide closer human disease parallels. CRISPR enables multiplexed edits and efficient generation of genetically modified organisms. Despite progress, challenges remain in improving specificity, delivery, and reducing off-target effects. Future developments aim to enhance precision, expand targeting capabilities, and improve therapeutic applications.CRISPR-based genome editing has transformed life sciences and human medicine by enabling precise modification of genetic material. This review discusses current CRISPR technologies, their limitations, and recent innovations. It highlights applications in human health and therapeutics, and outlines future developments. CRISPR-Cas9, derived from prokaryotic defense systems, revolutionized genome editing with its programmability and efficiency. It enables site-specific DNA cleavage, leading to gene knockouts, insertions, or deletions via DNA repair pathways. However, off-target effects and limited PAM requirements restrict its scope. Recent advancements include high-fidelity Cas9 variants, modified guide RNAs, and alternative PAM-targeting enzymes. Base and prime editing technologies allow precise single-nucleotide or small DNA sequence modifications without DSBs. These innovations enhance specificity and reduce off-target effects. CRISPR also enables transcriptional modulation through dCas9 fusions, allowing gene activation or suppression. RNA-guided Cas13 enzymes offer tools for RNA editing and modification. CRISPR applications span basic research, disease modeling, and therapeutic interventions, including gene therapy for genetic disorders. Ex vivo and in vivo approaches are being developed for clinical use. Large animal models, such as non-human primates, pigs, and dogs, provide closer human disease parallels. CRISPR enables multiplexed edits and efficient generation of genetically modified organisms. Despite progress, challenges remain in improving specificity, delivery, and reducing off-target effects. Future developments aim to enhance precision, expand targeting capabilities, and improve therapeutic applications.