IsNull([DocFileName] = True)
to
IsNull([DocFileName]) = True

Say the [DocFileName] is "Fred", replace that in your condition:
IsNull([DocFileName] = True) becomes IsNull("Fred" = True) which becomes IsNull(False) which is False

Try something like this.

If MadeNotesChk And IsNull(DocFileName) Then
    PickBtn.Enabled = True
    PickBtn.BackColor = RGB(100, 28, 30)
Else
    PickBtn.Enabled = False
End If

I would like someone to look at this again: This time I am providing all of the Code

On the Form I have CheckBox("MadeNoteChk"), Comand Button ("Pickbtn"), TextBox(DocFileName") and then a Command Button("Openbtn").

What I am trying do is:  if the MadeNotesChk is checked then enable the Pickbtn. After a Document is picked the name populates the DocFileName. At this point I would like the OpenBtn to be enabled and change color while Pickbtn is Disabled and changes color.

If for some reason the MadeNotesChk is unchecked  I want both Command Buttons to be disabled and the DocFileName set Null.

I am lot further than I was but I still can't get the button operate right in each condition.

Here is the code:

Details

Private Sub MadeNotesChk_Click()
If MadeNotesChk.Value = True Then
      
        If IsNull(DocFileName) = True Then
             PickBtn.Enabled = True
             PickBtn.BackColor = RGB(180, 90, 90)
             MsgBox "No Doc Enable PickBtn and change Color to Red"

        Else
             PickBtn.Enabled = False
             PickBtn.BackColor = RGB(50, 100, 150)
             OpenBtn.Enabled = True
             Me.OpenBtn.BackColor = RGB(180, 90, 90)
             MsgBox "Doc enables Pickbtn color blue and disable openbtn color red"

        End If

Else
    PickBtn.Enabled = False
    PickBtn.BackColor = RGB(50, 100, 150)
    OpenBtn.Enabled = False
    Me.OpenBtn.BackColor = RGB(50, 100, 150)
    Me.[DocFileName] = ""
    MsgBox "Not Check disable pick and open button color blue on both"
End If
    
End Sub

I have also tried putting the code in Form_Current and AfterUpdate for the CheckBox. I put the msg boxes in so I could tell were thing are working (or Not).

To start, Thanks Kevin for the input ( I am just learning about Sub Routines that you call from other subs. I haven't done this kind work for 30 years so I am really rusty, then I discovered Richard!
  
I had change this a little bit - It Sort of works, not the OpenBtn: I discovered if I go to next record and come back to the record the OpenBtn works.

I Added this -

Private Sub Form_Current()
    EnableDisableButtons
End Sub

And modified This -

Private Sub OpenBtn_Click()
'    MadeNotesChk = False 'This Didn't sim impact the effect on the button
    EnableDisableButtons
    FollowHyperlink CurrentProject.Path & "\documents\" & DocFileName
End Sub

So now I just need to discover why I have go to next then go back to the previous record for the button to work(I Thought the AfterUpdate would taken care of that. Any Thoughts?

I just wanted to thank folks' again and let you know how I solved the final issue. I had this problem where I had to go to the next record and then go to previous record to get the function to kick in.

I put a reference to the function in  the AfterUpdate event but still no luck. After putting MsgBoxes where every the function was called I discovered that AfterUpdate was never called.

Then I discovered the event  called "Enter". I put a reference the the function there and now all the buttons work correctly.