In　clinical　diagnostics,　as　well　as　food　and　environmental　safety　practices,　biosensors　are　powerful　tools　for　monitoring　biological　or　biochemical　processes.　Two-dimensional　(2D)　transition　metal　nanomaterials,　including　transition　metal　chalcogenides　(TMCs)　and　transition　metal　oxides　(TMOs),　are　receiving　growing　interest　for　their　use　in　biosensing　applications　based　on　such　unique　properties　as　high　surface　area　and　fluorescence　quenching　abilities.　Meanwhile,　nucleic　acid　probes　based　on　Watson-Crick　base　pairing　rules　are　also　being　widely　applied　in　biosensing　based　on　their　excellent　recognition　capability.　In　particular,　the　emergence　of　functional　nucleic　acids　in　the　1980s,　especially　aptamers,　has　substantially　extended　the　recognition　capability　of　nucleic　acids　to　various　targets,　ranging　from　small　organic　molecules　and　metal　ions　to　proteins　and　cells.　Based　on　pi-pi　stacking　interaction　between　transition　metal　nanosheets　and　nucleic　acids,　biosensing　systems　can　be　easily　assembled.　Therefore,　the　combination　of　2D　transition　metal　nanomaterials　and　nucleic　acids　brings　intriguing　opportunities　in　bioanalysis　and　biomedicine.　In　this　review,　we　summarize　recent　advances　of　nucleic　acid-functionalized　transition　metal　nanosheets　in　biosensing　applications.　The　structure　and　properties　of　2D　transition　metal　nanomaterials　are　first　discussed,　emphasizing　the　interaction　between　transition　metal　nanosheets　and　nucleic　acids.　Then,　the　applications　of　nucleic　acid-functionalized　transition　metal　nanosheet-based　biosensors　are　discussed　in　the　context　of　different　signal　transducing　mechanisms,　including　optical　and　electrochemical　approaches.　Finally,　we　provide　our　perspectives　on　the　current　challenges　and　opportunities　in　this　promising　field.　(C)　2016　Elsevier　B.V.　All　rights　reserved.