The article by Zhao and Haddad provides an overview of brain organoid protocols and their limitations. Brain organoids are three-dimensional (3D) clusters of cells grown in vitro that recapitulate the structural and functional properties of the brain in vivo. They can be derived from human tissue samples or stem cells and are used to study brain development, diseases, and drug screening. The generation of brain organoids involves 3D embryoid body formation, neural induction, differentiation, and maturation. Organoids can be generated through unguided or guided protocols, with the latter using extracellular matrix (ECM) scaffolds to support cell growth and specific signaling pathways to pattern organoids with region-specific identities. ECM embedding is widely used, but it can introduce variability and affect organoid development. Assembloids, which are combinations of multiple organoids with different regional identities, improve reproducibility and fidelity. However, organoids still lack the complexity of the human brain due to the absence of certain cell types and structures. Cellular stress, such as increased glycolysis and ER stress, is a significant challenge, and strategies like spinning bioreactors and higher oxygen levels have been used to mitigate this. The article also discusses the age equivalence of organoids to in vivo fetal brains, with 2-3-month-old organoids mimicking early to mid-fetal brain development and 10-month-old organoids reaching the transition stage between prenatal and postnatal development. Brain organoids have been used to model neurodevelopmental and neurodegenerative diseases, including autism spectrum disorders, Alzheimer's disease, and Parkinson's disease, providing valuable insights into disease mechanisms and potential therapeutic strategies. Despite their advancements, brain organoid technology faces limitations, such as the need for improved protocols to reduce variation and prevent cellular stress, and the challenge of extending organoid culture duration to better recapitulate later stages of brain development and aging.The article by Zhao and Haddad provides an overview of brain organoid protocols and their limitations. Brain organoids are three-dimensional (3D) clusters of cells grown in vitro that recapitulate the structural and functional properties of the brain in vivo. They can be derived from human tissue samples or stem cells and are used to study brain development, diseases, and drug screening. The generation of brain organoids involves 3D embryoid body formation, neural induction, differentiation, and maturation. Organoids can be generated through unguided or guided protocols, with the latter using extracellular matrix (ECM) scaffolds to support cell growth and specific signaling pathways to pattern organoids with region-specific identities. ECM embedding is widely used, but it can introduce variability and affect organoid development. Assembloids, which are combinations of multiple organoids with different regional identities, improve reproducibility and fidelity. However, organoids still lack the complexity of the human brain due to the absence of certain cell types and structures. Cellular stress, such as increased glycolysis and ER stress, is a significant challenge, and strategies like spinning bioreactors and higher oxygen levels have been used to mitigate this. The article also discusses the age equivalence of organoids to in vivo fetal brains, with 2-3-month-old organoids mimicking early to mid-fetal brain development and 10-month-old organoids reaching the transition stage between prenatal and postnatal development. Brain organoids have been used to model neurodevelopmental and neurodegenerative diseases, including autism spectrum disorders, Alzheimer's disease, and Parkinson's disease, providing valuable insights into disease mechanisms and potential therapeutic strategies. Despite their advancements, brain organoid technology faces limitations, such as the need for improved protocols to reduce variation and prevent cellular stress, and the challenge of extending organoid culture duration to better recapitulate later stages of brain development and aging.